Adverse Events Associated with Ingestion of Gamma-Butyrolactone
Minnesota, New Mexico, and Texas, 1998-1999

Products containing gamma-butyrolactone (GBL) * are marketed
for many
claimed purposes, including to induce sleep, release growth
hormone,
enhance sexual activity and athletic performance, relieve
depression, and
prolong life. GBL is converted by the body into
gamma-hydroxybutyrate
(GHB), a drug banned outside of clinical trials approved by the
Food and
Drug Administration (FDA). Recognized manifestations of GHB
toxicity
include bradycardia, hypothermia, central nervous system
depression, and
uncontrolled movements (1). This report describes seven cases of
GBL
toxicity involving the product "Revivarant," which is labeled as
containing
1.82 g of GBL per fluid ounce, reported from two hospital emergency
departments (EDs) in Minnesota during October-December 1998 and
summarizes
an additional 34 cases of GBL toxicity reported to poison centers
in New
Mexico and Texas during October 1998-January 1999.

Minnesota

Patient 1. On November 26, 1998, a 24-year-old man vomited and
had
seizures shortly after drinking 3-4 oz of Revivarant. His behavior
became
unusual, and he alternated between extreme agitation and profound
calm.
Paramedics noted that his skin was warm, flushed, and profusely
diaphoretic, and he had bradycardia (pulse as low as 45 beats per
minute
{bpm}). Systolic blood pressure was 110 mm Hg. Transcutaneous
oxygen
saturations (SpO2) were 96% on room air, and blood glucose by
fingerstick
was 90 mg/dL. During transport to an ED, he had periods of
combativeness
lasting 30 to 60 seconds followed by coma lasting 1-3 minutes. In
the ED,
he was unconscious with spontaneous eye opening, a positive
withdrawal
reflex, and no speech (Glasgow Coma Scale of 7); rectal temperature
was
94.8 F (34.9 C). A urine toxicology screen and blood ethanol test
were
negative. He was intubated and admitted to the intensive-care unit
(ICU)
with a diagnosis of toxic encephalopathy. During the next 7 hours,
his
heart rate increased from 42 to 116 bpm and he became more alert.
He had no
recollection of events except for having ingested Revivarant. He
was
discharged with normal mental status.

Patient 2. On December 12, 1998, a 46-year-old woman had a
seizure and
lost consciousness after drinking approximately 2.7 oz of
Revivarant in
conjunction with ethanol. Paramedics found her unconscious and in
severe
respiratory depression with a pulse of 54 bpm. Oxygen was
administered by
mask; she had an SpO2 of 87%. On arrival in the ED, physical
examination
identified sinus bradycardia (54 bpm); temperature of 96.1 F (35.6
C); and
miotic pupils. A serum ethanol level was 0.11%. She was admitted to
the
ICU, mechanically ventilated through the night, and awoke in
improved
condition the next morning; she was discharged with no memory of
the
events.

Patient 3. On November 8, 1998, a 31-year-old man drank
approximately
1 oz of Revivarant, four beers, and a large sip of wine. Shortly
thereafter, he gradually lost consciousness and subsequently fell.
He
regained consciousness but had involuntary muscle movements and
episodes of
confusion. Paramedics noted that he was ambulatory but confused. On
physical examination in the ED, he was agitated, anxious, and
unable to
recall the preceding events. His shoulders twitched, and he had a
small
abrasion below his left eye. He had a pulse of 64 bpm and
hypothermia (oral
temperature of 95.2 F {35.1 C}). Breath ethanol level was 0.08%. He
denied
previous GBL use or illicit drug use. He recovered completely and
was
discharged.

Patients 4 and 5. On October 31, 1998, a 24-year-old man
(patient 4)
and a 26-year-old man (patient 5) each drank 10-13 oz of Revivarant
while
drinking alcohol at a bar. On leaving the bar, witnesses observed
them fall
and become unresponsive. On arrival at the ED, they alternated
between
somnolence and confusion. When awake, neither patient could
consistently
follow commands. Patient 4 had fecal incontinence. Vital signs for
both
patients were within normal limits. Breath ethanol levels were
0.09%
(patient 4) and 0.15% (patient 5). Neither patient had a history of
using
medications or illicit drugs. After 2 hours of observation, the
patients
recovered but were unable to recall most of the evening's events.

Patients 6 and 7. On December 12, 1998, a 19-year-old woman
(patient
6) and a 22-year-old woman (patient 7) were brought to an ED by
friends
because of vomiting and decreased levels of consciousness. These
symptoms
followed ingestion of Revivarant (2 oz by patient 6 and an unknown
amount
by patient 7). Patient 6 had drank one beer; patient 7 had had no
ethanol.
Vital signs were normal except for respiratory depression. On
physical
examination, patient 6 was lethargic and disoriented. Patient 7
exhibited
intermittent periods of extreme agitation, necessitating chemical
treatment
and physical restraint, punctuated by moments of calm during which
her
attention focused on minor details. Mental changes for both
patients
resolved, and they were discharged approximately 4 hours after
arrival.

New Mexico

From October 3, 1998, through January 29, 1999, the New Mexico
Poison
Center identified 14 cases of adverse events resulting in an ED
visit among
persons who had ingested GBL-containing products. Ten (71%) of the
cases
were reported in January. Patients' ages ranged from 14 to 36
years; nine
were male. Products used included "Firewater" (11 cases), "Blue
Nitro
Vitality" (two), and "RenewTrient" (one). The approximate amount
ingested
ranged from 1 to 10 oz (mean: 3 oz). Five (36%) persons also had
ingested
ethanol and/or other drugs. Most of the patients were discharged
from the
ED within 13 hours of arrival; three were hospitalized. The most
common
symptoms and signs were nausea/vomiting (10 {71%}), obtundation
(nine
{64%}), bradycardia (seven {50%}), prolonged unconsciousness (six
{43%}),
syncope (six {43%}), seizures (four {29%}), confusion (four {29%}),
combativeness (four {29%}), respiratory depression (three {21%}),
amnesia
(two {14%}), and euphoria (two {14%}). One person had cardiac
arrest, one
had respiratory arrest, and one had a motor-vehicle crash
associated with
the effects resulting from use of a GBL-containing product. No
deaths were
reported.

Texas

From October 2, 1998, through January 24, 1999, Texas
poison-control
centers identified 20 adverse events resulting in ED visits among
persons
who had ingested GBL-containing products. Twelve (60%) of the cases
were
reported in January. Patients' ages ranged from 11 to 41 years; 13
were
male. Products known to have been used included "RenewTrient" (six
cases),
"Revivarant" (four), "Revivarant-G" (two), and "Blue Nitro
Vitality" (two).
Ten persons also ingested ethanol and/or other drugs. Ten patients
were
admitted to the hospital from the ED. The most common symptoms and
signs
were obtundation (13 {65%}), prolonged unconsciousness (nine
{45%}),
respiratory depression (nine {45%}), anxiety/nervousness (seven
{35%}),
nausea/vomiting (six {30%}), confusion (six {30%}),
tremors/twitching (four
{20%}), tachycardia (three {15%}), and combativeness (three {15%}).
One
person had respiratory arrest; no deaths were reported.

Editorial Note

Editorial Note: GBL is metabolized to GHB in the body, but because
of
better absorption GBL has greater bioavailability than GHB on an
equimolar
basis (2). Clinical effects of GHB appear to be dose-related and
include
reports of vomiting, hypotonia, tremors, seizures, aggression,
impairment
of judgment, coma, respiratory depression, hypothermia, and
bradycardia
(1). GHB mixed with ethanol acts synergistically to produce central
nervous
system and respiratory depression (3). Symptoms usually resolve
with
supportive care within 2-96 hours (4). Death occurring when GHB was
the
sole intoxicant also has been reported (5). Toxic effects of GBL
would be
expected to be similar or identical to those of GHB, but previous
clinical
experience is limited (6,7). There is no antidote for GHB;
treatment
consists of supportive therapy until symptoms of toxicity subside.
A
withdrawal syndrome, which can include insomnia, tremor, and
anxiety, has
been reported following discontinuance of GHB in chronic, high-dose
users
(8).

GBL is an industrial and household solvent of acrylate
polymers, and
unintentional poisonings have been reported (6,9). It also is
marketed as a
dietary supplement at health food stores and on the World-Wide Web
under
several trade names. Although labeled as dietary supplements,
GBL-containing products are illegally marketed, unapproved new
drugs that
have been involved in at least 55 reports of adverse events,
including one
death (10). On January 21, 1999, FDA asked manufacturers to recall
their
GBL-containing products and warned consumers through press releases
to
avoid taking these products (10). Public education efforts should
inform
consumers that FDA review procedures for drugs are different than
those
used for dietary supplements. Consumers should be alert to the
potential
dangers of these products and understand that terms such as
"natural" do
not necessarily imply safety. Physicians should counsel patients
about
these products and be prepared to recognize and treat the toxic
reactions
that some might produce. Chronic GBL users should be monitored for
withdrawal symptoms when discontinuing use of the product.
Depending on the
severity of the withdrawal symptoms, medical intervention may be
required.
Physicians are encouraged to report serious adverse events
associated with
these products to FDA's MedWatch program, telephone (800) 332-1088.

Also is known as dihydro-2(3H)-furanone; 4-butanolide;
2(3H)-furanone,
dihydro; tetrahydro-2-furanone; and butyrolactone gamma.

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